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Details

Stereochemistry ACHIRAL
Molecular Formula C13H18Br2N2O.C9H10N4O4
Molecular Weight 616.303
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMBROXOL ACEFYLLINATE

SMILES

CN1C2=C(N(CC(O)=O)C=N2)C(=O)N(C)C1=O.NC3=C(Br)C=C(Br)C=C3CN[C@H]4CC[C@H](O)CC4

InChI

InChIKey=IPUHJDQWESJTGD-PFWPSKEQSA-N
InChI=1S/C13H18Br2N2O.C9H10N4O4/c14-9-5-8(13(16)12(15)6-9)7-17-10-1-3-11(18)4-2-10;1-11-7-6(8(16)12(2)9(11)17)13(4-10-7)3-5(14)15/h5-6,10-11,17-18H,1-4,7,16H2;4H,3H2,1-2H3,(H,14,15)/t10-,11-;

HIDE SMILES / InChI

Molecular Formula C13H18Br2N2O
Molecular Weight 378.103
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula C9H10N4O4
Molecular Weight 238.2001
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800035262 | https://www.ncbi.nlm.nih.gov/pubmed/23158495 | https://www.ncbi.nlm.nih.gov/pubmed/18482096 | https://www.ncbi.nlm.nih.gov/pubmed/19578116 | http://zywiebio.com/drug-development/therapeutic-areas-of-interest/gaucher-disease/

Ambroxol, a substituted benzylamine, is an active metabolite of bromhexine, which is itself a synthetic derivative of vasicine, the active principle extracted from the plant species Adhatoda vasica. Ambroxol is an expectorant exerting mucokinetic properties, mucociliary activity, stimulation of surfactant production, anti-inflammatory and antioxidative actions and the local anaesthetic effect. Ambroxol was discovered at and has been manufactured by Dr. Karl Thomae GmbH, a division of Boehringer Ingelheim. The ambroxol patent is expired and the drug is available as a generic product from many different companies. Ambroxol was originally developed by Boehringer Ingelheim as a OTC therapy for respiratory disorders related to excessive mucus. Ambroxol's indication is secretolytic therapy in acute and chronic bronchopulmonary diseases associated with abnormal mucus secretion and impaired mucus transport. Boehringer Ingelheim markets the product under various brand names such as Mucosolvan® and Lasolvan®. Ambroxol was identified and found to be a pH-dependent, mixed-type inhibitor of glucocerebrosidase (GCase). Its inhibitory activity was maximal at neutral pH, found in the endoplasmic reticulum, and undetectable at the acidic pH of lysosomes. The pH dependence of Ambroxol to bind and stabilize the enzyme was confirmed. Ambroxol increases both the lysosomal fraction and the enzymatic activity of several mutant GCase variants. This profile of Ambroxol would allow to bind and stabilize GCase in the endoplasmic reticulum (thus preventing its degradation within endoplasmic reticulum), but without affecting GCase in the lysosomes (thus allowing it to degrade glucosylceramide). Indeed, studies showed that Ambroxol treatment significantly increased N370S and F213I mutant GCase activity and protein levels in fibroblasts originally obtained from Gaucher patients. Gaucher's disease is caused by the deficiency of glucocerebrosidase; ambroxol is a chaperone that acts by binding to and stabilising glucocerebrosidase. Zywie (formerly ExSAR Corporation) and Belrose Pharma are developing ambroxol hydrochloride (BEL 0218) for the treatment of type III Gaucher's disease. .

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
MUCOSOLVAN

Approved Use

MUCOSOLVAN (ambroxol hydrochloride) is indicated for secretolytic therapy in acute and chronic bronchopulmonary diseases associated with abnormal mucus secretion and impaired mucus transport.
PubMed

PubMed

TitleDatePubMed
Modulating effects of mucoregulating drugs on the attachment of Haemophilus influenzae.
2001 Mar
[Effect of ambroxol on lipid peroxidation in homogenates of the human placenta].
2001 Oct
Efficacy and tolerability of ambroxol hydrochloride lozenges in sore throat. Randomised, double-blind, placebo-controlled trials regarding the local anaesthetic properties.
2002
Immunoassay screening of lysergic acid diethylamide (LSD) and its confirmation by HPLC and fluorescence detection following LSD ImmunElute extraction.
2002 Apr
Depressant effect of ambroxol on stimulated functional responses and cell death in rat alveolar macrophages exposed to silica in vitro.
2002 Feb
[Mucolytics in acute and chronic respiratory tract disorders. II. Uses for treatment and antioxidant properties].
2002 Mar
Ambroxol inhibits peroxynitrite-induced damage of alpha1-antiproteinase and free radical production in activated phagocytic cells.
2002 Sep
Inhibition of bleomycin-induced cell death in rat alveolar macrophages and human lung epithelial cells by ambroxol.
2003 Oct 1
Ambroxol reduces LPS toxicity mediated by induction of alkaline phosphatases in rat lung.
2004 Aug
[A near-infrared diffuse reflectance analysis method for the noninvasive quantitative analysis of ambroxol hydrochloride tablets].
2004 Jan
Inhibition of inflammatory responses by ambroxol, a mucolytic agent, in a murine model of acute lung injury induced by lipopolysaccharide.
2004 Jan
Secretory leukoprotease inhibitor and pulmonary surfactant serve as principal defenses against influenza A virus infection in the airway and chemical agents up-regulating their levels may have therapeutic potential.
2004 Nov
Simultaneous determination of roxithromycin and ambroxol hydrochloride in a new tablet formulation by liquid chromatography.
2004 Sep 3
Differences in tidal breathing between infants with chronic lung diseases and healthy controls.
2005 Sep 8
The influence of ambroxol and capsaicin on the isolated rabbit bladder wall.
2005 Sep-Oct
[Ambroxol].
2006
Systematic review of clinical data with BNO-101 (Sinupret) in the treatment of sinusitis.
2006 Apr
The influence of variation of gastric pH on the gelation and release characteristics of in situ gelling pectin formulations.
2006 Apr 7
[Efficacy of intravenous or atomizing ambroxol for prevention of respiratory distress syndrome in preterm infants].
2006 Aug
Herbal medicines for the treatment of COPD: a systematic review.
2006 Aug
[Ambroxol-induced toxicoderma].
2006 Feb
D-MEKK1, the Drosophila orthologue of mammalian MEKK4/MTK1, and Hemipterous/D-MKK7 mediate the activation of D-JNK by cadmium and arsenite in Schneider cells.
2006 Feb 1
[Influence of ambroxol on paraquat-induced lung tissue injury and change of pulmonary surfactant-associated protein A in the experimental rats].
2006 Jun
Ambroxol for the prevention of acute upper respiratory disease.
2006 Jun
[Atomization inhalation of ambroxol as an auxiliary therapy for severe pneumonia in neonates].
2006 Jun
Comparison of the effects of four Na+ channel analgesics on TTX-resistant Na+ currents in rat sensory neurons and recombinant Nav1.2 channels.
2006 Mar 13
Ambroxol-induced modification of ion transport in human airway Calu-3 epithelia.
2006 May 5
[Ambroxol-induced immune hemolytic anemia].
2006 Oct
Safety and usage pattern of an over-the-counter ambroxol cough syrup: a community pharmacy-based cohort study.
2006 Sep
Simultaneous determination and pharmacokinetic study of roxithromycin and ambroxol hydrochloride in human plasma by LC-MS/MS.
2007 Jul
Determination of ambroxol in human plasma by high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/ESI).
2007 Jun 15
[Determination of ambroxol and clenbuterol in human plasma by LC-MS/MS method].
2007 Mar
Parenteral ambroxol treatment causes xanthine and calcium oxalate stones in rats.
2007 May
Solid-state chemistry of ambroxol theophylline-7-acetate.
2007 May
Patents

Sample Use Guides

In Vivo Use Guide
Adults: daily dose of 30 mg (one Ambroxol tablet ) to 120 mg (4 Ambroxol tablets) taken in 2 to 3 divided doses Children up to 2 years: half a teaspoonful Ambroxol syrup twice daily Children 2 - 5 years: half a teaspoonful Ambroxol syrup 3 times daily Children over 5 years: One teaspoonful Ambroxol syrup 2-3 times daily.
Route of Administration: Oral
Ambroxol exerted a biphasic response in surfactant secretion, with a significant increase at low concentrations (1 - 10 uM) and an inhibition at high concentrations (≥ 0.1 mM), which is beyond reported plasma Ambroxol concentrations in blood
Substance Class Chemical
Created
by admin
on Thu Jul 06 02:22:17 UTC 2023
Edited
by admin
on Thu Jul 06 02:22:17 UTC 2023
Record UNII
0HM1E174TN
Record Status Validated (UNII)
Record Version
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Name Type Language
AMBROXOL ACEFYLLINATE
MART.   WHO-DD  
Common Name English
Ambroxol Theophyllinate [WHO-DD]
Common Name English
ACEBROPHYLLINE
Common Name English
AMBROMUCIL
Common Name English
7H-PURINE-7-ACETIC ACID, 1,2,3,6-TETRAHYDRO-1,3-DIMETHYL-2,6-DIOXO-, COMPD. WITH TRANS-4-(((2-AMINO-3,5-DIBROMOPHENYL)METHYL)AMINO)CYCLOHEXANOL (1:1)
Systematic Name English
AMBROXOL THEOPHYLLINATE
Common Name English
BRONCOMNES
Common Name English
SURFOLASE
Common Name English
CYCLOHEXANOL, 4-(((2-AMINO-3,5-DIBROMOPHENYL)METHYL)AMINO)-, TRANS-, MONO(1,2,3,6-TETRAHYDRO-1,3-DIMETHYL-2,6-DIOXO-7H-PURINE-7-ACETATE) (SALT)
Systematic Name English
AMBROXOL ACEFYLLINATE [MART.]
Common Name English
AMBROXOL-THEOPHYLLINE-7-ACETATE
Common Name English
Ambroxol acefyllinate [WHO-DD]
Common Name English
Code System Code Type Description
RXCUI
186010
Created by admin on Thu Jul 06 02:22:17 UTC 2023 , Edited by admin on Thu Jul 06 02:22:17 UTC 2023
ALTERNATIVE
RXCUI
236595
Created by admin on Thu Jul 06 02:22:17 UTC 2023 , Edited by admin on Thu Jul 06 02:22:17 UTC 2023
PRIMARY RxNorm
FDA UNII
0HM1E174TN
Created by admin on Thu Jul 06 02:22:17 UTC 2023 , Edited by admin on Thu Jul 06 02:22:17 UTC 2023
PRIMARY
CAS
96989-76-3
Created by admin on Thu Jul 06 02:22:17 UTC 2023 , Edited by admin on Thu Jul 06 02:22:17 UTC 2023
PRIMARY
DRUG BANK
DB13141
Created by admin on Thu Jul 06 02:22:17 UTC 2023 , Edited by admin on Thu Jul 06 02:22:17 UTC 2023
PRIMARY
EVMPD
SUB12842MIG
Created by admin on Thu Jul 06 02:22:17 UTC 2023 , Edited by admin on Thu Jul 06 02:22:17 UTC 2023
PRIMARY
EPA CompTox
DTXSID60914235
Created by admin on Thu Jul 06 02:22:17 UTC 2023 , Edited by admin on Thu Jul 06 02:22:17 UTC 2023
PRIMARY
SMS_ID
100000089018
Created by admin on Thu Jul 06 02:22:17 UTC 2023 , Edited by admin on Thu Jul 06 02:22:17 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
PARENT -> SALT/SOLVATE
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ACTIVE MOIETY